Registration Dossier

Administrative data

Description of key information

Studies conducted to recognised training guidelines with GLP. In vitro studies waived as in vivo studies available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-03-31, 1987-04-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: approx. 12-14 weeks
- Weight at study initiation: 2520 - 2720 g
- Housing: individually in metal cages
- Diet: Ad libitum, standard rabbit pellet (Nafag No. 814, Gossau, Switzerland)
- Water: Ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light):12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Tween 80
Controls:
no
Amount / concentration applied:
An amount of 0.5 g of test article was applied on a gauze patch. This patch was moistened with Tween 80 before application.
Duration of treatment / exposure:
4 h
Observation period:
72 h, Since no skin reactions were observed the study was discontinued after 72 h.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: Gauze patch (20 cm ) loosely covered with an aluminum foil (36 cm ) and held in place by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).

SCORING SYSTEM
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Total possible erythema score 4

Edema formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Total possible edema score 4

EVALUATION CRITERIA (according to EEC Directive No. 83/467/ July 29, 1983)
Corrosion criteria
A substance or a preparation is considered to be corrosive if, when it is applied to healthy intact animal skin, it produces full thickness destruction of skin tissue on at least one animal during the test for skin irritation.

Irritation criteria
A substance or a preparation is considered to be irritant if it causes inflammation of the skin or ocular lesions corresponding to the evaluation of the parameters given below:

Inflammation of the skin
which persists for at least 24 hours after an exposure period of up to four hours and corresponds to the following values determined on the rabbit according to the cutaneous irritation test method cited in Annex V:
- the mean value of the scores for either erythema and eschar formation or edema formation, calculated over all the animals tested, is two or more,
- or, in the case where the Annex V test has been completed using three animals, either erythema and eschar formation or edema formation equivalent to a mean value of two or more calculated for each animal separately has been observed in two or more animals.
In both cases all scores at each of the reading times (24, 48, and 72 hours) for an effect should be used in calculating the respective mean values.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
After dermal application of 0.5 g test article moistened with Tween 80 to male rabbits for 4 h according to OECD 404 (1981) no erythema or edema were observed. Therefore, the test article is considered to be not irritating to rabbit skin according to EU 67/548/EEC Directive and EC/1272/2008.
Other effects:
A slight loss of body weight was observed in animal No. 102 on day 3.

Bodyweight of animals in grams

Animal no. / sex

101 / male

102 / male

103 / male

At start of study

2650

2720

2520

At end of study (3 d)

2690

2630

2610

Interpretation of results:
GHS criteria not met
Conclusions:
No indication of skin irritation was observed over the duration of the test. The test material is considered not to be a skin irritant.
Executive summary:

In this guideline (OECD 404) study conducted to GLP standards, the test material (EC 404-360-3) was determined to be not irritating to skin. 0.5g of the test material was moistened with Tween 80 on a semiocclusive patch before being applied to male rabbits for 4 hours. As no erythema or edema were observed at the 24, 48, or 72 hour observation periods, the test material is not classified as irritating to skin according to CLP regulation 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-04-28, 1987-05-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: approx. 12-14 weeks
- Weight at study initiation: 2190 - 2420 g
- Housing: Individually in metal cages
- Diet: Ad libitum, standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: Ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as control.
Amount / concentration applied:
0.1 mL of undiluted test material (corresponding to 38 mg) was applied.
Duration of treatment / exposure:
72 h; The treated eye was not rinsed.
Observation period (in vivo):
1, 24, 48, 72 h
Number of animals or in vitro replicates:
3
Details on study design:
The irritant/corrosive potency was scorred according to the EEC commission directive No. 83/467, 1983. For further details see additional information.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Corneal opacity graded 1 was observed 1 h after application.
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Corneal opacity graded 1 was observed 1 h after application.
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Iritis graded 1 was observed 1h after application.
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Redness of conjunctiva graded 1 was observed 1 h after application.
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Conjunctival redness graded 2 was observed 1 h after application.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Chemosis graded 1-2 was observed 1 h after application.
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Chemosis graded 1-2 was observed 1 h after application.
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Chemosis graded 1-2 was observed 1 h after application.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material invoked no meaningful indications of irritation over the duration of the test. The test material is not considered an eye irritant.
Executive summary:

In this guideline (OECD 405) study conducted to GLP standards, the test material (EC 404-360-3) was determined to be not irritating to eyes. Undiluted test material (0.1 ml, corresponding to 38 mg) was applied directly to an eye of three rabbits with the other eye of each being the control. The conditions of the eyes were then observed at 1, 24, 48 and 72 hours. At 1 hour, only slight effects graded 1 or 2 were observed. After 24 hours conjunctival redness graded 1 was observed in one animal only, this was fully reversible over the duration of the test. Thus, according to CLP regulation 1272/2008, this substance is not classified for eye irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

After dermal application of 0.5 g test article moistened with Tween 80 to male rabbits for 4 h according to OECD 404 (1981) no erythema or edema was observed.

When 0.1 mL (corresponding to 38 mg) test article was placed into an eye of each of three rabbits according to OECD 405 (1981) without rinsing slight effects (graded 1), were seen at reading time point 1h. After 24 h the only effect reported was conjunctival redness graded 1 in one animal.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008.